具有设计取代方式多糖硫酸酯的合成及其生物应答效应研究

项目名称： 具有设计取代方式多糖硫酸酯的合成及其生物应答效应研究

项目编号： No.21204073

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 高分子科学

项目作者： 王俊龙

作者单位： 西北师范大学

项目金额： 25万元

中文摘要： 本项目立足西部丰富的圆头蒿种籽废渣资源，以提取纯化的圆头蒿多糖（ASP）为原料，针对高分子量及多分支结构ASP的黏度大、溶解性小、生物利用性差以及多糖硫酸酯合成产物结构的不可控等问题，通过催化体系的引入和基团保护技术，建立反应模型，优化工艺，进行沙蒿多糖硫酸酯（SASP）区域选择性合成。利用现代仪器分析手段确定SASP的取代度（DS）、单糖组成、分子量、分支度和取代位置等化学结构；通过对多糖溶液构象的表征，阐明糖链化学结构变化对溶液构象及其转变方式的影响。体外培养肿瘤细胞，对不同结构的SASP进行体外抗肿瘤活性研究，探讨SASP的化学结构及溶液构象对其体外抗肿瘤活性应答效应的规律，明确构效关系，为活性多糖衍生物药物分子的合成和结构设计提供依据。

中文关键词： 多糖；硫酸化；区域选择性；溶液构象；构效关系

英文摘要： Artemisia sphaerocephala was widely distributed in western China. In our previous study, A. sphaerocephala polysaccharide (ASP) was extracted from waste residue of A. sphaerocephala seed after oil press. The application of ASP was limited due to its high viscosity, low solubility and poor bioavailability. Most reports had studied the nonselective synthesis of sulfated polysaccharides. In this project, group protection methods and catalyst system were employed for region-selective synthesis of sulfated ASP (SASP). The reaction parameters were optimized by Box-Behnken design. The primary structure of SASP such as degree of substitution (DS), monosaccharide composition, molecular weight, branch degree and substitution position were determined by modern instrumental analysis. The relationship between primary structure and solution conformation was also studied. Furthermore, anti-tumor activities of SASP were evaluated in vitro for a better understanding of the relationship between structure and biological response effects. This study could provide evidence for design and synthesis of carbohydrate-modified drugs.

英文关键词： polysaccharide；sulfation； region-selective；solution conformation；structure-activity relationship